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Dengue Virus

Dengue fever is caused by any of four closely related members of the Flavivirus family that are most prevalent in the tropical and subtropical countries. Within the United States, the disease is endemic in Puerto Rico and outbreaks have occurred in Key West, Florida. The mosquitoes known to transmit dengue virus, Aedes aegypti and Aedes albopictus, are present throughout much of the southeastern United States and infected returning travelers may pose a risk for initiating local transmission. Indigenous transmission has been documented in Texas.

Most dengue virus infections are asymptomatic, but some patients may develop either dengue fever or the more severe dengue hemorrhagic fever. The incubation period from infection to onset of symptoms is three days to two weeks. Dengue fever is a self-limited acute illness that lasts for 2 to 7 days and includes fever, rash, myalgia, and arthralgia. Leukopenia is common.

A small proportion of patients develop dengue hemorrhagic fever, which is characterized by resolving fever, thrombocytopenia, bleeding and increased vascular permeability evidenced by hemoconcentration, hypoalbuminemia or hypoproteinemia, ascites, or pleural effusion. Dengue hemorrhagic fever can result in circulatory instability or shock.

IgM antibodies directed against dengue virus envelope protein typically develop during the first week of illness and may persist in serum for months or years after initial infection. Neutralizing IgG antibodies develop shortly after IgM antibodies and persist for multiple years. IgG antibodies confer long-lived immunity. In persons previously infected with or vaccinated against a flavivirus, subsequent infection with another flavivirus can result in both a diminished IgM response and a rapid increase in neutralizing antibodies against multiple flaviviruses.

For patients with suspected dengue virus disease, nucleic acid amplification tests (NAATs) are preferred because interpretation of serologic test results is complicated by cross-reactivity and difficulty determining the timing of infection. Dengue IgM antibody may crossreact with other flaviviruses such as West Nile, St. Louis encephalitis, Japanese encephalitis and yellow fever viruses.

For symptomatic nonpregnant persons, dengue virus NAAT should be performed on serum collected 7 days or less after symptom onset. Real time polymerase chain reaction (RT-PCR) can detect all four serotypes of dengue virus. Dengue virus IgM antibody testing should be performed on NAAT-negative serum specimens or serum collected greater than 7 days after onset of symptoms.

Specimen Days from Onset Preferred Test
Acute 0 – 7 RT-PCR
Convalescent 8 – 30 Dengue IgM


For symptomatic pregnant women, serum specimens should be collected as soon as possible within 12 weeks of symptom onset for concurrent dengue and Zika virus NAATs and IgM antibody testing. Positive IgM antibody test results with negative NAAT results should be confirmed by neutralizing antibody tests.

For serum specimens collected less than 7 days after onset of symptoms, the combination of a negative NAAT result and negative IgM antibody testing suggests the patient did not have a recent flavivirus infection. However, in the absence of NAAT testing, a negative acute IgM antibody test might be due to specimen collection before development of detectable antibodies and does not rule out infection. For specimens collected from 7 days to 12 weeks after onset of symptoms, a negative IgM antibody result to dengue virus rules out recent infection. Other etiologies should be considered.

Plaque reduction neutralization tests (PRNTs) are quantitative assays that measure virus-specific neutralizing antibody titers for dengue and other flaviviruses. PRNTs can resolve false-positive antibody results caused by nonspecific reactivity. CDC uses a 90% cutoff value titer of 10 or higher in serum and 2 or higher in cerebrospinal fluid to define positive specimens. Negative PRNT titers against dengue virus in a serum specimen collected greater than 7 days after illness onset rule out infection.

Pregnant women with a clinically compatible illness and recent possible exposure to dengue and Zika virus should have concurrent diagnostic testing for dengue and Zika virus infection performed by NAAT and IgM antibody testing on a serum specimen and NAAT on a urine specimen to diagnose Zika virus infection. Specimens should be collected as soon as possible for dengue and Zika virus NAATs and within 12 weeks of symptom onset for Zika virus NAAT. A positive NAAT result on any specimen typically provides evidence of recent infection. However, if NAAT is only positive for Zika virus on a single specimen and IgM antibody testing is negative, the NAAT should be repeated on newly extracted RNA from the same specimen to rule out false-positive test results.

If both dengue and Zika virus NAATs are negative but either IgM antibody test is positive, confirmatory PRNTs should be performed against dengue, Zika, and other flaviviruses endemic to the region where exposure occurred. For indeterminate IgM antibody results, IgM antibody testing should be repeated on the same specimen or PRNTs performed. If IgM antibody results are positive for one virus but the assay for the other virus was not performed, the second assay should be performed to appropriately interpret results. If the second assay is not performed, the single positive result should be interpreted as a presumptive flavirivus infection.


Sharp TM, Fischer M, Muñoz-Jordán JL, et al. Dengue and Zika Virus Diagnostic Testing for Patients with a Clinically Compatible Illness and Risk for Infection with Both Viruses. MMWR Recomm Rep 2019;68(No. RR-1):1–10. DOI: icon

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